Linked Life Data

11777335

Source:http://linkedlifedata.com/resource/pubmed/id/11777335

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-1-4
pubmed:abstractText
Human skin fibroblasts were cultured long-term in the presence of ascorbic acid to allow formation of a three-dimensional collagen matrix, and the effects of this on activation of secreted matrix metalloproteinase-2 (MMP-2) were examined. Accumulation of collagen over time correlated with increased levels of both mature MMP-2 and cell-associated membrane type 1-MMP (MT1-MMP), and subsequently increased mRNA levels for MT1-MMP, providing temporal resolution of the "nontranscriptional" and "transcriptional" effects of collagen on MT-1MMP functionality. MMP-2 activation by these cultures was blocked by inhibitors of prolyl-4-hydroxylase, or when fibroblasts derived from the collagen alpha1(I) gene-deficient Mov-13 mouse were used. MMP-2 activation by the Mov-13 fibroblasts was rescued by transfection of a full-length alpha1(I) collagen cDNA, and to our surprise, also by transfection with an alpha1(I) collagen cDNA carrying a mutation at the C-proteinase cleavage, which almost abrogated fibrillogenesis. Although studies with ascorbate-cultured MT1-MMP-/- fibroblasts showed that MT1-MMP played a significant role in the collagen-induced MMP-2 activation, a residual MT1-MMP-independent activation of MMP-2 was seen which resembled the level of MMP-2 activation persisting when wild-type fibroblasts were cultured in the presence of both ascorbic acid and MMP inhibitors. We were also unable to block this residual activation with inhibitors specific for serinyl, aspartyl, or cysteinyl enzymes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Ascorbic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Collagen, http://linkedlifedata.com/resource/pubmed/chemical/Collagen Type I, http://linkedlifedata.com/resource/pubmed/chemical/Cross-Linking Reagents, http://linkedlifedata.com/resource/pubmed/chemical/Fibrillar Collagens, http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 14, http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 2, http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinases..., http://linkedlifedata.com/resource/pubmed/chemical/Metalloendopeptidases, http://linkedlifedata.com/resource/pubmed/chemical/Mmp14 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Procollagen-Proline Dioxygenase
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0014-4827
pubmed:author
pubmed:copyrightInfo
(c)2001 Elsevier Science.
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
272
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
109-18
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
MT1-MMP-dependent and -independent regulation of gelatinase A activation in long-term, ascorbate-treated fibroblast cultures: regulation by fibrillar collagen.
pubmed:affiliation
VBCRC Breast Cancer Invasion and Metastasis Unit, St. Vincent's Institute of Medical Research, Melbourne, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't